Four areas of work with nerve growth factor (NGF) have been under investigation and will provide the focus for future experimentation: 1) Chemical modification of NGF; 2) Biosynthesis of NGF; 3) Function of central nervous system receptors; and 4) Function of end organ receptors. Chemical modification of lysine by three different routes indicate that this residue is not required for activity. Further, when the subunits are cross-linked covalently through lysine, the derivative obtained shows identical binding properties as native I125-NGF including negatively cooperative binding. Examination of derivatives in which 1, 2, and 3 tryptophan residues have been modified indicates that even the inactive 2 and 3 oxidized derivatives still have largely unaltered binding properties. The sequence of N. naja NGF has been completed to the extent of about 70 percent degree of identity with mouse NGF. Collaborative studies (with Dr. E. Shooter) have indicated a close degree of similarity in function with mouse NGF. However it will not form a 7S complex. Experiments to demonstrate that the biosynthetic product of NGF is a larger polypeptide chain than the 118 residue unit usually isolated have been only partially successful. The specific binding receptors in chick embryonic brain are located largely in the synaptosomal fraction and appear during development on a course parallel to that of synaptogenesis. However, some early receptors appear that seem to be located on the cell bodies. Such receptors would correspond to those responsible for the tectal transformation from 7 to 8 day specificity that has been demonstrated for NGF with tectal cells in culture (in collaboration of Dr. L. Glaser). Characterization of the receptors in embryonic chick heart has be initiated. BIBLIOGRAPHIC REFERENCES: R.A. Hogue-Angeletti, R.A. Bradshaw, andd W.A. Frazier, "Nerve Growth Factor: Structure and Mechanism of Action", Adv. in Metabolic Disorders, Vol. 8, "Somatomedins and Some Other Growth Factors" (R. Luft and K. Hall, Eds.)., Academic Press, New York (1975), pp. 285-299.